It has been an obligation for pharmaceutical manufacturing that every production lot is subjected to endotoxin test. Furthermore, it has been a general technical knowledge that a medical implement and a cell-culturing apparatus also should be managed in terms of endotoxin. The present invention facilitates secure completion of such a test for even a small amount of a specimen, allowing reduction in amount of the specimen to test and an examination reagent to use.
A specimen is generally measured with a reagent (examination agent) after the reagent is manually transferred from the holding bottle to a cell. However, this manual procedure is inevitably accompanied by many troubles such as a scattering of reagent, a contaminating foreign substance, and an inaccurately weighed reagent. Thus, in recently increasing manners, the reagent is automatically transferred into the cell. Alternatively, a cell vial has been known to allow an examination that is free from transferring the reagent into the cell and can be simply completed by putting the specimen into the vial with the reagent held in beforehand.
Meanwhile, the endotoxin test for every production lot of a specimen medicine has been conventionally carried out by a pyrogen test in which a test rabbit is administered in vivo with the specimen medicine to monitor daily the change in body temperature. However, to confirm the test result needs 2-3 days up to a lifted temperature and an amount of the specimen as much as 20,000 μl to 50,000 μl and is accompanied by the problem of lacking reliability. Additionally, the test has a problem that it costs too much due to the fed rabbit and the observation labor after administration.
Recently, the endotoxin test has been quickly and securely carried out by utilizing a method in which a hemocyte component-containing solution from a horseshoe crab (hereinafter, abbreviated to an AL solution) is reacted with endotoxin to give an enzyme (such as protease), of which the activation reaction or the coagulation is then used as a base to measure an endotoxin concentration in the specimen. Furthermore, in order to automatically confirm the gelation reaction, an instrument such as a toxinometer (made by Wako Pure Chemical Industries, Ltd.) has been developed to facilitate a toxicity test. The toxinometer is generally used to examine a specimen by a method in which a light emitting diode is used irradiate light to the flat part (the straight part, in other words, the problem-free part for optical measurement) in the side surface of a vial with the specimen held in.
Conventionally, glass vial has been produced by such method as: a blowing method in which a lump of glass poured from melting vessel is shut in a separable molding die and air pressure forms the shape; a horizontal method in which a raw material tube elongated in perfect circle is laid in transversal position to be processed; and a vertical method in which a raw material tube is placed in upright position to be processed. However, there has been only horizontal method conventionally for making a bottom part to be thick.
That is, in order to make the bottom part to be thick, it was necessary that a vial with thin bottom was formed in a vertical method, and thereafter the bottom part was to be burnt in a horizontal method. In other words, conventional method was two processes method which required position change of a vial, that is, thin bottom was formed in a vertical method and then the bottom part was made to be thick in a horizontal method.
In addition, since the above mentioned conventional method utilizes horizontal method, the shape of inner plane of thick bottom vial could be formed to be convex round state only in downward direction.
FIG. 1(A) shows a conventional manufacturing method of another vial. A slender pipe is held upright placing the bottle opening in upward position, the lowest end opening thereof is heated to be melt while the pipe is rotating, and compressed air is blown from the bottle opening, so that bottom part of the bottle is formed. A vial which is formed in this way has such configuration that, as shown in FIG. 2(A), both of the inner surface and the outer surface of the bottom is formed in a shape protruding downwardly in round state.
When liquid specimen is poured into a vial obtained by these conventional manufacturing methods, the light irradiated at the bottom part is distorted as the bottom part is formed to be round. Consequently, the light has to be irradiated in a smooth part (a straight part, in other words a part which has no hindrance for optical measurement). For that reason, there have been such problems as the position of light irradiation had to be in a position as high as possible from the bottom, and the amount of specimen was required as much as 1,000 to 2,000 μl at least to secure a lighting position without any hindrance for examination due to generation of meniscus at the upper surface of the liquid due to surface tension. Whereby, there has been such a problem that the amount of reagent usage is required in large quantity.
Moreover, there was a risk of examination error due to hindrance at the optical examination (measurement) caused by contamination of foreign substances when transferring endotoxin examination reagent into examination cell.